Trisubstituted organophosphorus compounds are of great importance as ligands in homogeneous catalysis. Variation of the substituents on the phosphorus in such compounds enables the electronic and steric properties of the phosphorus ligand to be influenced in a targeted way, so that selectivity and activity in homogeneously catalyzed processes can be controlled. Enantiomerically enriched chiral ligands are used in asymmetric synthesis and asymmetric catalysis, and in this case it is important that the electronic properties and the stereochemical properties of the ligand are optimally matched to the respective catalysis problem. There is therefore a great need for chiral ligands which differ stereochemically and/or electronically in order to discover ligands which have been optimally xe2x80x9ctailoredxe2x80x9d to a particular asymmetric catalytic reaction. In the ideal case, it is therefore desirable to have a chiral ligand framework which can be modified in a wide variety of ways and can be varied within a wide range in respect of its steric and electronic properties.
The structural variety of the phosphorus ligands known hitherto is very wide. These ligands can be classified, for example, according to classes of compounds, and examples of such classes of compounds are trialkylphosphines and triarylphosphines, phosphites, phosphinites, phosphonites, aminophosphines, etc. This classification according to classes of compounds is particularly useful for describing the electronic properties of the ligands.
Alternatively, phosphorus ligands can be classified according to their symmetry properties or according to the xe2x80x9cdenticityxe2x80x9d of the ligands. This structuring takes account, in particular, of the stability, activity and (potential) stereoselectivity of metal complexes with phosphorus ligands as catalyst precursors/catalysts. Apart from the widespread C2-symmetric bidentate ligand systems such as DUPHOS, DIOP, BINAP or DEGUPHOS, unsymmetrical bidentate organophosphorus ligands are becoming increasingly significant in asymmetric catalysis. Important examples are the large class of versatile chiral ferrocenylphosphine ligands such as JOSIPHOS, for example, the aminophosphine-phosphinite ligands such as PINDOPHOS or DPAMPP which are used particularly successfully in the asymmetric hydrogenation of olefins, or phosphine-phosphite ligands such as BINAPHOS or BIPHEMPHOS, which represent milestones in the asymmetric hydroformylation of olefins. An important aspect of the success of these classes of compounds is ascribed to the creation of a particularly asymmetric environment of the metal center by means of these ligand systems. To utilize such an environment for effective transfer of the chirality, it is advantageous to control the flexibility of the ligand system as inherent limitation of the asymmetric induction.
The present invention describes novel, unsymmetrical, bidentate and chiral phosphorus ligand systems which in a unique way combine the above-described important features for effective asymmetric induction. They create both a highly asymmetric coordination sphere with organophosphorus donors which can be modified independently of one another, and they can be modified simply over an extraordinarily wide range in terms of their steric and electronic properties. Furthermore, they allow gradual adjustment of the rigidity by means of a change in the basic structure of the xe2x80x9cligand backbonexe2x80x9d. At the same time, in contrast to many established ligand systems, the compounds of the invention can be obtained via simple syntheses over a wide range of variations.
The present invention relates to unsymmetric bidendate organophosphorus ligands of the formula (I) which have a modular structure and have a trivalent phosphine function and a second trivalent phosphorus group which is bound via a heteroatom to a chiral ligand framework,
R1R2PZC*HR3XP(YR4)(YR5)xe2x80x83xe2x80x83(I)
where
R1-R5 are identical or different and are each a hydrogen atom or a C1-C50 group such as C1-C24-alkyl, C2-C24-alkenyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, C6-C14-aryl, phenyl, naphthyl, fluorenyl, C2-C13-heteroaryl in which the number of heteroatoms, in particular from the group consisting of N, O, S, can be 1-4, where the cyclic aliphatic or aromatic radicals are preferably 5- to 7-membered rings and the specified substituents can each bear one or more substituents selected independently from the group consisting of hydrogen, C1-C20-alkyl, C2-C20-alkenyl, C1-C10-haloalkyl, C3-C8-cyclo-alkyl, C3-C8-cycloalkenyl, C2-C8-heteroalkyl, C1-C9-heteroalkenyl, C6-C14-aryl, phenyl, naphthyl, fluorenyl, C2-C7-heteroaryl in which the number of heteroatoms, in particular from the group consisting of N, O, S, can be 1-4, C1-C10-alkoxy, C1-C9-trihalomethylalkyl, trifluoromethyl, trichloromethyl, fluoro, chloro, bromo, iodo, nitro, hydroxy, trifluoromethylsulfonato, oxo, thio, thiolato, amino, C1-C8-substituted amino of the forms mono-, di-, tri-C1-C8-alkylamino or C2-C8-alkenylamino or mono-, di-, tri- C6-C8-arylamino or C1-C8-alkyl-C6-C8-arylamino, cyano, carboxyl, carboxylato of the formula COOR8, where R8 is a monovalent cation or a C1-C8-alkyl group, C1-C8-acyloxy, sulfinato, sulfonato of the formula SO3R8, phosphato of the formula PO3H2, PO3HR8, PO3R82, tri-C1-C6-alkylsilyl, and where two of the substituents can also be bridged and R1 and R2 or R4 and R5 can be joined to one another so as to form a 4-8-membered cyclic compound,
X is xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94 or xe2x80x94NR5xe2x80x94,
R6 is a radical as defined for R1-R5,
Y is a direct phosphorus-carbon bond, xe2x80x94Oxe2x80x94 or xe2x80x94NR7xe2x80x94, where
R7 is a radical as defined for R1-R5,
Z represents one to six carbon atoms which are joined by single or double bonds and link the phosphine unit PR1R2 to the carbon center C*, where Z is part of an aliphatic, cycloaliphatic, olefinic, cycloolefinic system which may contain heteroatoms, preferably nitrogen, oxygen or sulfur, a metallocene, in particular 1,1xe2x80x2- or 1,2-disubstituted ferrocene, or particularly preferably an aromatic or heteroaromatic ring system which may be unsubstituted or be substituted by one or more substituents as indicated for R1-R5 or directly substituted by C1-C10-alkoxy, C1-C9-trihalomethylalkyl, trifluoromethyl, trichloromethyl, fluoro, chloro, bromo, iodo, nitro, hydroxy, trifluoromethylsulfonato, oxo, thio, thiolato, amino, C1-C8-substituted amino of the formulae NH2, NH-alkyl-C1-C8, NH-aryl-C5-C6, N-(alkyl-C1-C8)2, N-(aryl-C5-C6)2, N-(alkyl-C1-C8)3+, N-(aryl-C5-C6)3+, cyano, carboxylato of the formulae COOH and COOR8, where R8 is either a monovalent cation or C1-C8-alkyl, C1C6-acyloxy, sulfinato, sulfonato of the formulae SO3H and SO3R8, where R8 is either a monovalent cation, C1-C8-alkyl or C6-aryl, phosphonato, phosphato of the formulae PO3H2, PO3HR8 and PO3R82, where R8 is either a monovalent cation, C1-C8-alkyl or C6-aryl, C1-C6-trialkylsilyl, CONH2, NHCO-alkyl-C1-C4, CON(alkyl-C1-C8)2, CO-alkyl-C1-C8, COO-alkyl-C1-C8, CO-alkenyl-C1-C8, NHCOO-alkyl-C1-C4, CO-aryl-C6-C10, COO-aryl-C6-C10, CHCHxe2x80x94COO-alkyl-C1-C8, CHCHCOOH and
P is trivalent phosphorus.
The invention also relates to complexes comprising such a chiral ligand system of the formula (I) with at least one metal.
R1-R5 are each preferably, independently of one another, a C1-C20-alkyl, alkenyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl radical, each of which may be substituted by one or more substituents selected from the group consisting of C1-C20-alkyl, C2-C20-alkenyl, C1-C10-haloalkyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, C6-C14-aryl, C2-C7-heteroaryl, C1-C10-alkoxy, halo, nitro, hydroxy, oxo, thio, thiolato, amino, substituted amino, cyano, sulfonato, tri-C1-C6-alkylsilyl, where two of the substituents may also be bridged.
Preference is given to compounds in which Z is part of a ring system. R3 is not part of this ring system. Preference is given to three- to nine-membered ring systems. Particular preference is given to five- to seven-membered ring systems. The ring system can contain from one to four heteroatoms, preferably from one to two heteroatoms, which are preferably selected from among O, N and S. Sulfur S can be present in various oxidation states, preferably xe2x80x94Sxe2x80x94 or xe2x80x94SO2xe2x80x94. The nitrogen of the ring system can be present as NR, NR2+, NRH+, NC(O)R, NSO2R, NO(O)R2, where R is alkyl or aryl. The ring systems can be directly substituted by one or more substituents as indicated for R1-R5 or by alkoxy, halo, nitro, hydroxy, oxo, thio, thiolato, amino, substituted amino, cyano, sulfonato, phosphonato, trialkylsilyl groups, where the substituents can also be bridged to one another.
Preferred ring systems are phenyl, cyclopentyl, cyclohexyl, pyridyl, pyrrole, furyl, thiophene, tetrahydrofuran, tetrahydrothiophene, piperidyl, pyrrolidinyl, ferrocenyl, dioxolane or sulfolane rings which may be unsubstituted or substituted as described above. For the purposes of the present invention, metallocenes such as ferrocenes are formally included among aromatics.
In the ligand system of the present invention, R1-R7 preferably comprise, independently of one another, alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkoxy, trialkylsilyl or/and dialkylamino groups having from 1 to 20, in particular from 1 to 6, carbon atoms.
Among alkyl substituents, preference is given to methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, n-heptyl, n-octyl, n-nonyl, n-decyl.
Among cyclic alkyl substituents, particular preference is given to substituted and unsubstituted cyclopentyl, cyclohexyl, cycloheptyl.
Preferred alkenyl radicals are vinyl, propenyl, isopropenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 2-pentenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 3-methyl-1-butenyl, 1-hexenyl, 1-heptenyl; 2-heptenyl, 1-octenyl or 2-octenyl. Among cyclic alkenyl substituents, particular preference is given to cyclopentenyl, cyclohexenyl, cycloheptenyl and norbornyl.
Among aryl substituents in R1-R7, particular preference is given to 2-alkylphenyl, 3-alkylphenyl, 4-alkylphenyl, 2,6-dialkylphenyl, 3,5-dialkylphenyl, 3,4,5-trialkylphenyl, 2-alkoxyphenyl, 3-alkoxyphenyl, 4-alkoxyphenyl, 2,6-dialkoxyphenyl, 3,5-dialkoxyphenyl, 3,4,5-trialkoxyphenyl, 3,5-dialkyl-4-alkoxyphenyl, 3,5-dialkyl-4-dialkylaminophenyl, 4-dialkylamino, where the abovementioned alkyl and alkoxy groups preferably each contain from 1 to 6 carbon atoms, 3,5-trifluoromethyl, 4-trifluoromethyl, 2-sulfonyl, 3-sulfonyl, 4-sulfonyl or monohalogenated to tetrahalogenated phenyl and naphthyl. Preferred halogen substituents are F, Cl and Br.
All haloalkyl or/and haloaryl groups preferably have the formulae CHal3, CH2CHal3, C2Hal, where Hal can be, in particular, F, Cl and Br. Particular preference is given to haloalkyl or/and haloaryl groups of the formulae CF3, CH2CF3, C2F5.
Preference is given to systems in which when X is NR61 Y is a direct phosphorus-carbon bond, and when X is O, Y is either a direct phosphorus-carbon bond or xe2x80x94Oxe2x80x94. Finally, ligand systems of the formula I enriched in one enantiomer are preferred as optically active ligand systems. Particular preference is given to ligand systems whose enantiomeric enrichment exceeds 90%, in particular 99%.
A number of routes are available for synthesizing these compounds of the formula (I):
The choice of a reaction route is dependent on the availability of the corresponding starting materials and on the desired substitution pattern. In the following, an illustrative selection will be presented by way of example to indicate the variety of ligand systems obtainable by means of the novel process described here, without ruling out alternative synthetic routes and other substitution patents and ligand frameworks of the type (I). In the following description, the substituents R and Rxe2x80x2 represent different substituents specified more precisely in the above definition of R1-R5. In the interests of clarity, simple ligand frameworks such as phenyl or ethylene have been chosen in the illustrations, without thereby implying restrictions or limitations.
The synthetic principle for six basic structures of the type (I) is described below.
Variation of methods which are known in principle makes it possible to obtain phosphine alcohols and phosphineamines of the type III, V, VII, VIII, X and XI (schemes 2-4) in a few synthesis steps. These routes will be described briefly for the purposes of illustration.
Chiral alcohols of the type II (scheme 1) (obtainable by various asymmetric reduction methods. Hydrogenation: e.g. Noyori et al., Tetrahedron Letters, 1991, 32, 4163; J. Am. Chem. Soc. 1998, 120, 13529; hydride reduction: e.g. Corey et al., J. Am. Chem. Soc. 1987, 109, 5551) can, after introduction of a suitable alcohol-protecting group SG (e.g. methoxymethylene, Fuji et al., Synthesis, 1975, 276; tetrahydropyranyl, Weiss et al., J. Org. Chem. 1979, 44, 1438), be metallated and subsequently quenched with the desired chlorophosphine (Brunner et al., J. Chem. Soc., Perkin Trans. 1, 1996). After splitting off the protecting group SG under acid conditions, the desired chiral phosphinoalcohol, illustrated by structure III in FIG. 1, is obtained. 
The corresponding chiral aminophosphines of the type V (scheme 2) are obtainable via a similar reaction sequence. Starting from chiral amines of the type IV (obtainable according to processes known in principle by means of various asymmetric reduction methods (hydrogenation: Burk et al., J. Org. Chem. 1998, 63, 6084; J. Am. Chem. Soc. 1996, 118, 5142; hydride transfer: Mukaiyama et al., Chem. Lett. 1997, 493; enzymatically: Santaniello et al., Chem. Rev. 1992, 92, 1071)), after N-alkylation and protection of the NH function, the compounds are phosphinated as above and the secondary aminophosphine V is subsequently set free. 
Aminophosphines and hydroxyphosphines having a ferrocenyl bridge (VII and VIII) (scheme 3) are likewise obtainable by modification of known synthesis strategies. Starting from enatiomerically pure aminoferrocenylphosphine (VI) (synthesis, for example: Hayashi and Kumada, Bull. Chem. Soc. Jpn., 1980, 53, 53, 1138), the corresponding sec-hydroxyferrocenylphosphines (VII) or aminoferrocenylphosphines (VIII) can be obtained with retention of the configuration by means of various nucleophilic substitution reactions (methods analogous to Ugi et al., J. Org. Chem. 37, 3052, and Hayashi and Kumada, Bull. Chem. Soc. Jpn., 1980, 53, 1138). 
Borane-protected hydroxyphosphines having an alkyl bridge (X) (scheme 4) can be prepared by enantioselective diorganozinc addition onto phosphinylaldehydes (IX) using a method analogous to Brunner et al. (Tetrahedron Lett. 1998, 54, 10317). Corresponding aminophosphines (XI) can be obtained from the phosphinylaldehydes (IX) by reductive amination with primary amines and subsequent resolution of the racemate. 
According to the invention, the conversion of the aminophosphines and hydroxyphosphines III, V, VII, VIII into the novel ligand systems XII-XVII of the formula (I) (scheme 5) occurs in one step by addition of chlorophosphines or chlorophosphites in the presence of stoichiometric amounts of a base (methods for substitution reactions of this type: e.g. Reetz et al., Angew. Chem. 1999, 111, 134; RajanBabu et al., J. Org. Chem. 1997, 62, 6012; Onuma et al., Bull. Chem. Soc. Jpn. 1980, 53, 2012). For the compounds of the type X and XI, subsequent removal of the protective borane group, e.g. by means of amines, is necessary. 
According to the invention, ligands of the type 1 in which the substituents R1, R2, R4 and R5 are identical can, as an alternative, be prepared in a single-vessel process starting from the corresponding haloalcohols of the type II by reaction with 2 equivalents of a strong base (e.g. tert-butyllithium) and subsequent reaction with 2 equivalents of the corresponding chlorophosphines (scheme 6). 
The compounds of the formula (I) can be used as ligands on metals in asymmetric, metal-catalyzed reactions (e.g. hydrogenation, hydroformylation, rearrangement, allylic alkylation, cyclopropanation, hydrosilylation, hydride transfers, hydroboration, hydrocyanation, hydrocarboxylation, aldol reactions or the Heck reaction) and also in polymerizations. They are particularly suitable for asymmetric reactions.
Suitable complexes, in particular of the formula (XVIII), comprise novel compounds of the formula (I) as ligands,
[MxPmLnSq]Arxe2x80x83xe2x80x83(XVIII)
where, in the formula (XVIII), M is a metal center, preferably a transition metal center, L are identical or different coordinating organic or inorganic ligands and P are novel bidentate organophosphorus ligands of the formula (I), S are coordinating solvent molecules and A are equivalents of noncoordinating anions, and x and m are integers greater than or equal to 1, n, q and r are integers greater than or equal to 0.
An upper limit is imposed on the sum m+n+q by the coordination sites available on the metal centers, with not all coordination sites having to be occupied. Preference is given to complexes having an octahedral, pseudooctahedral, tetrahedral, pseudotetrahedral, square planar coordination sphere, which may also be distorted, around the respective transition metal center. In such complexes, the sum m+n+q is less than or equal to 6x.
The complexes of the invention contain at least one metal atom or ion, preferably a transition metal atom or ion, in particular one selected from the group consisting of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel and copper.
Preference is given to complexes having less than four metal centers, particular preferably ones having one or two metal centers. The metal centers can be occupied by different metal atoms and/or ions.
Preferred ligands L in such complexes are halide, in particular Cl, Br and I, diene, in particular cyclooctadiene, norbornadiene, olefin, in particular ethylene and cyclooctene, acetato, trifluoroacetato, acetylacetonato, allyl, methallyl, alkyl, in particular methyl and ethyl, nitrile, in particular acetonitrile and benzonitrile, and also carbonyl and hydrido ligands.
Preferred coordinating solvents S are amines, in particular triethylamine, alcohols, in particular methanol, and aromatics, in particular benzene and cumene.
Preferred noncoordinating anions A are trifluoroacetate, trifluoromethanesulfonate, BF4, ClO4, PF6, SbF6 and BAr4.
In the individual complexes, different molecules, atoms or ions can be present in the individual constituents M, P, L, S and A.
Among the complexes having an ionic structure, preference is given to compounds of the type [RhP(diene)]+Axe2x88x92, where P is a novel ligand of the formula (I).
These metal-ligand complexes can be prepared in situ by reaction of a metal salt or an appropriate precursor complex with the ligands of the formula (I). Furthermore, a metal-ligand complex can be obtained by reaction of a metal salt or an appropriate precursor complex with the ligands of the formula (I) and subsequent isolation.
Examples of metal salts are metal chlorides, bromides, iodides, cyanides, nitrates, acetates, acetylacetonates, hexafluoroacetylacetonates, tetrafluoroborates, perfluoroacetates and triflates, in particular of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel or/and copper.
Examples of precursor complexes are: cyclooctadienepalladium chloride, cyclooctadienepalladium iodide, 1,5-hexadienepalladium chloride, 1,5-hexadienepalladium iodide, bis(dibenzylidene-acetone)palladium, bis(acetonitrile)palladium(II) chloride, bis(acetonitrile)palladium(II) bromide, bis(benzonitrile)palladium(II) chloride, bis(benzonitrile)palladium(II) bromide, bis(benzonitrile)palladium(II) iodide, bis(allyl)palladium, bis(methallyl)palladium, allylpalladium chloride dimer, methallylpalladium chloride dimer, tetramethylethylene-diaminepalladium dichloride, tetramethylethylene-diaminepalladium dibromide, tetramethylethylenediamine-palladium diiodide, tetramethylethylenediamine-dimethylpalladium, cyclooctadieneplatinum chloride, cyclooctadieneplatinum iodide, 1,5-hexadieneplatinum chloride, 1,5-hexadieneplatinum iodide, bis(cyclooctadiene)platinum, potassium ethylenetrichloroplatinate, cyclooctadienerhodium(I) chloride dimer, norbornadienerhodium(I) chloride dimer, 1,5-hexadienerhodium(I) chloride dimer, tris(triphenylphosphine)rhodium(I) chloride, hydrido-carbonyltris(triphenylphosphine)rhodium(I) chloride, bis(cyclooctadiene)rhodium(I) perchlorate, bis(cyclooctadiene)rhodium(I) tetrafluoroborate, bis(cyclooctadiene)rhodium(I) triflate, bis(acetonitrile)cyclooctadienerhodium(I) perchlorate, bis(acetonitrile)cyclooctadienerhodium(I) tetrafluoroborate, bis(acetonitrile)cyclooctadienerhodium(I) triflate, cyclopentadienerhodium(III) chloride dimer, pentamethylcyclopentadienerhodium(III) chloride dimer, (cyclooctadiene)Ru(xcex73-allyl)2, ((cyclooctadiene)Ru)2(acetate)4, ((cyclooctadiene)Ru)2(trifluoroacetate)4, RuCl2(arene) dimer, tris(triphenylphosphine)ruthenium(II) chloride, cyclooctadieneruthenium(II) chloride, OsCl2(arene) dimer, cyclooctadieneiridium(I) chloride dimer, bis(cyclooctene)iridium(I) chloride dimer, bis(cyclo-octadiene)nickel, (cyclododecatriene)nickel, tris(norbornene)nickel, nickel tetracarbonyl, nickel (II) acetylacetonate, (arene)copper triflate, (arene)copper perchlorate, (arene)copper trifluoroacetate, cobalt carbonyl.
The complexes based on one or more metals, in particular those selected from the group consisting of Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, may themselves be catalysts or can be used for preparing catalysts based on one or more metals, in particular those selected from the group consisting of Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu. All these complexes are suitable for hydrogenation, hydroformylation, rearrangement, allylic alkylation, cyclopropanation, hydrosilylation, hydride transfer reactions, hydroboration, hydrocyanation, hydrocarboxylation, aldol reactions or the Heck reaction. The complexes of the invention are particularly useful in the asymmetric hydrogenation of
Cxe2x95x90C, Cxe2x95x90O or Cxe2x95x90N bonds, in which they have high activities and selectivities, and in asymmetric hydroformylation. In particular, it is here advantageous that the ligands of the formula (I) can be very well matched to the respective substrate and the catalytic reaction in terms of their steric and electronic properties due to the simple and wide-ranging manner in which they can be modified.
Corresponding catalysts comprise at least one of the complexes of the invention.